Absence of behavioral abnormalities and neurodegeneration in vivo despite widespread neuronal huntingtin inclusions.

ABSTRACT: We have serendipitously established a mouse that expresses an N-terminal human huntingtin (htt) fragment with an expanded polyglutamine repeat (approximately 120) under the control of the endogenous human promoter (shortstop). Frequent and widespread htt inclusions occur early in shortstop mice. Despite these inclusions, shortstop mice display no clinical evidence of neuronal dysfunction and no neuronal degeneration as determined by brain weight, striatal volume, and striatal neuronal count. These results indicate that htt inclusions are not pathogenic in vivo. In contrast, the full-length yeast artificial chromosome (YAC) 128 model with the identical polyglutamine length and same level of transgenic protein expression as the shortstop demonstrates significant neuronal dysfunction and loss

SUBMITTER: Slow EJ 

PROVIDER: S-EPMC1183566 | biostudies-literature | 2005 Aug

REPOSITORIES: biostudies-literature